Leinster's Robbie Henshaw and Dan Leavy will not be able to put their weight behind Ireland's tussle with France this Sunday (KO3.0, Virgin Media 1 & ITV).
Centre Henshaw has been frustrated by a dead leg that was expected to have cleared up by now.
The same uncertainty has blighted Leavy's return from a calf issue.
The flanker has been out since December and been mysteriously slow in his rehabilitation.
They probably won't be the only ones as Joey Carbery is up against the clock to recover from a hamstring strain.
At least, Garry Ringrose has finally shaken off his hamstring problem to surely come straight back in for Ireland.
Jordan Larmour and the Munster trio of CJ Stander, Andrew Conway and Tadhg Beirne have all returned to the squad.
Meanwhile, France coach Jacques Brunel has kept the faith with the same team that manhandled Scotland 27-10 at Stade de France. Their first win of the campaign should inject confidence where previously there had been none.
There are just five players retained from last year's dramatic 15-13 loss to Ireland in Paris.
Interestingly, they all come in the forward pack with captain Guilhem Guirado, loose-head Jefferson Poirot, second row Sebastien Vahaamahina and flankers Wenceslas Lauret and Arthur Iturria.
The half-backs Antoine Dupont and Romain N'Tamack could be there for the next decade.
Mathieu Bastareaud has always been problematic for the Irish, even for Brian O'Driscoll and Gordon D'Arcy.
The array of attacking weapons around the hulking centre will ask questions of Ireland's concentrations.
FRANCE (v Ireland): T Ramos; D Penaud, M Bastareaud, G Fickou, Y Huget; R N'Tamack, A Dupont; J Poirot, G Guirado (capt), D Bamba, F Lambey, S Vahaamahina, W Lauret, A Iturria, L Picamoles.
Replacements: C Chat, E Falgoux, D Aldegheri, P Willemse, G Alldritt; B Serin, A Belleau, M Medard.